The immune system protects us from foreign pathogens and must distinguish between “self” (elements of the body that belong to us) and “non-self”. Pathogens, such as viruses, bacteria, fungi antigens, are “non-self”. Auto-reactive lymphocytes are abnormal cells of the immune system that can destroy “self”.

Apoptosis, natural programmed cell death, is a major way that immune system tolerance is regulated. When apoptosis pathways are not working, auto-reactive lymphocytes are not cleared, leading to autoimmunity. Apoptosis causes DNA fragmentation, shrinkage and formation of an “apoptotic body” to be reabsorbed. External and internal stimulation can trigger apoptosis. On cell surfaces, an area called the “death domain” can be stimulated. Internally, apoptosis can be caused by DNA damage or metabolic imbalance.

Transient autoimmune responses are normal, persistent reactions are abnormal. There must be some tolerance of abnormal cells, especially in bone marrow and thymus. Cells that escape destruction in the bone marrow and thymus can be destroyed in the blood. Those not destroyed can cause autoimmune disease. Genetic and environmental factors are involved with more autoimmunity in monozygotic twins.

Apoptosis is important in lymphocyte maturation for the removal of lymphocytes still present and activated after an immune response is over. During apoptosis, cell fragments are presented to the immune system and can trigger the development of auto-antigens.

In Grave’s thyroid disease, auto-antibodies target specific proteins. In systemic lupus erythematosis (SLE), multiple organs are involved. Antibodies target DNA, phospholipids and various proteins. Two organ specific autoimmune diseases, such as thyroid disease and vitiligo, can occur in one patient. Two different systemic autoimmune diseases, such as SLE and Sjogren’s syndrome, can occur in one patient.

Young females are more susceptible to autoimmune disease. The immune protected parts of the human body are the lens, testis and reproductive organs; and pregnant women are protected from auto-immunity.

CONCLUSION: Defects in the apoptosis pathways may cause autoimmune disease in susceptible people, in which the immune system is unable to differentiate between “self” and “non-self”.

NOTE: Read about prolactin as a marker of autoimmune disease and the role of prolactin in apoptosis.

To read the author’s abstract of the article click on the link to the author’s title of the article above.

PMID: 18220747.

Summary #235.